Abstract
Stress is an important factor known to increase alcohol and drug relapse risk. This paper examines the stress-related processes that influence addiction relapse. First, individual patient vignettes of stress-and cue-related situations that increase drug seeking and relapse susceptibility are presented. Next, empirical findings from human laboratory and brain-imaging studies that are consistent with clinical observations and support the specific role of stress processes in the drug-craving state are reviewed. Recent findings on differences in stress responsivity in addicted versus matched community social drinkers are reviewed to demonstrate alterations in stress pathways that could explain the significant contribution of stress-related mechanisms on craving and relapse susceptibility. Finally, significant implications of these findings for clinical practice are discussed, with a specific focus on the development of novel interventions that target stress processes and drug craving to improve addiction relapse outcomes.
Similar content being viewed by others
References and Recommended Reading
Sinha R: How does stress increase risk of drug abuse and relapse? Psychopharmacology (Berl) 2001, 158:343–359.
Sinha R: Stress and drug abuse. In Handbook of Stress and the Brain, part 2. Stress: Integrative and Clinical Aspects, vol. 15. Edited by Steckler T, Kalin NH, Reul JM. Amsterdam: Elsevier; 2005:333–356.
Hughes JR: Tobacco withdrawal in self-quitters. J Consult Clin Psychol 1992, 60:689–697.
Kouri EM, Pope HG, Jr, Lukas SE: Changes in aggressive behavior during withdrawal from long-term marijuana use. Psychopharmacology (Berl) 1999, 143:302–308.
Mulvaney FD, Alterman AI, Boardman CR, Kampman K: Cocaine abstinence symptomatology and treatment attrition. J Subst Abuse Treat 1999, 16:129–135.
Budney AJ, Hughes JR: The cannabis withdrawal syndrome. Curr Opin Psychiatry 2006, 19:233–238.
Kreek MJ, Koob GF: Drug dependence: stress and dysregulation of brain reward pathways. Drug Alcohol Depend 1998, 51:23–47.
Koob GF, Ahmed SH, Boutrel B, et al.: Neurobiological mechanisms in the transition from drug use to drug dependence. Neurosci Biobehav Rev 2004, 27:739–749.
Volkow N, Fowler JS: Addiction, a disease of compulsion and drive: involvement of the orbitofrontal cortex. Cereb Cortex 2000, 10:318–325.
Kalivas PW, Volkow ND: The neural basis of addiction: a pathology of motivation and choice. Am J Psychiatry 2005, 162:1403–1413.
McLellan AT, Luborsky L, Woody GE, et al.: Predicting response to drug and alcohol abuse treatments: role of psychiatric severity. Arch Gen Psychiatry 1983, 40:620–625.
Carroll KM, Power MD, Bryant KJ, Rounsaville BJ: One year follow-up status of treatment-seeking cocaine abusers: psychopathology and dependence severity as predictors of outcome. J Nerv Ment Dis 1993, 181:71–79.
Tennant F, Shannon JA, Nork JG, et al.: Abnormal adrenal gland metabolism in opioid addicts: implications for clinical treatment. J Psychoactive Drugs 1991, 23:135–149.
Doherty K, Kinnunen T, Militello FS, Garvey AJ: Urges to smoke during the first month of abstinence: relationship to relapse and predictors. Psychopharmacology (Berl) 1995, 119:171–178.
Killen J, Fortmann SP: Craving is associated with smoking relapse: findings from three prospective studies. Exp Clin Psychopharmacol 1997, 5:137–142.
Baker TB, Brandon TH, Chassin L: Motivational influences on cigarette smoking. Annu Rev Psychol 2004, 55:463–491.
Contoreggi C, Herning RI, Na P, et al.: Stress hormone responses to corticotropin-releasing hormone in substance abusers without severe comorbid psychiatric disease. Biol Psychiatry 2003, 54:873–878.
Adinoff B, Junghanns K, Kiefer F, Krishnan-Sarin S: Suppression of the HPA axis stress-response: implications for relapse. Alcohol Clin Exp Res 2005, 29:1351–1355.
McDougle CJ, Black JE, Malison RT, et al.: Noradrenergic dysregulation during discontinuation of cocaine use in addicts. Arch Gen Psychiatry 1994, 51:713–719.
Krystal JH, Webb E, Cooney NL, et al.: Serotonergic and noradrenergic dysregulation in alcoholism: M-chrophenyl-piperazine and yohimbine effects in recently detoxified alcoholics and healthy comparison subjects. Am J Psychiatry 1996, 153:83–92.
Bar KJ, Boettger MK, Neubauer R, et al.: Heart rate variability and sympathetic skin response in male patients suffering from acute alcohol withdrawal syndrome. Alcohol Clin Exp Res 2006, 30:1592–1598.
Rechlin T, Orbes I, Weis M, Kaschka WP: Autonomic cardiac abnormalities in alcohol-dependent patients admitted to a psychiatric department. Clin Auton Res 1996, 6:119–122.
Ingjaldsson JT, Laberg JC, Thayer JF: Reduced heart rate variability in chronic alcohol abuse: relationship with negative mood, chronic thought suppression, and compulsive drinking. Biol Psychiatry 2003, 54:1427–1436.
Little KY, Zhang KL, Desmond T, et al.: Striatal dopaminergic abnormalities in human cocaine users. Am J Psychiatry 1999, 156:238–245.
Staley JK, Hearn WL, Ruttenber AJ, et al.: High affinity cocaine recognition sites on the dopamine transporter are elevated in fatal cocaine overdose victims. J Pharmacol Exp Ther 1994, 271:1678–1685.
Malison R, Best SE, van Dyck CH, et al.: Elevated striatal dopamine transporters during acute cocaine abstinence as measured by [123I] beta-CIT SPECT. Am J Psychiatry 1998, 155:832–834.
Letchworth SR, Nader MA, Smith HR, et al.: Progression of changes in dopamine transporter binding site density as a result of cocaine self-administration in rhesus monkeys. J Neurosci 2001, 21:2799–2807.
Beveridge T, Smith H, Nader M, Porrino L: Effects of chronic cocaine self-administration on norepinephrine transporters in the nonhuman primate brain. Psychopharmacology (Berl) 2005, 180:781–788.
Dackis CA, Gold MS: New concepts in cocaine addiction: the dopamine depletion hypothesis. Neurosci Biobehav Rev 1985, 9:469–477.
Tiffany S: A cognitive model of drug urges and drug-use behavior: the role of automatic and non-automatic processes. Psychol Rev 1990, 97:147–168.
O’Brien CP, Childress AR, Ehrman RN, Robbins SJ: Conditioning factors in drug abuse: can they explain compulsion? J Psychopharmacol 1998, 12:15–22.
Robinson TE, Berridge KC: The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Brain Res Rev 1993, 18:247–291.
Robinson TE, Berridge KC: The psychology and neurobiology of addiction: an incentive-sensitization view. Addiction 2000, 95(Suppl 2):S91–S117.
Stewart J, de Wit H, Eikelboom R: Role of unconditioned and conditioned drug effects in the self-administration of opiates and stimulants. Psychol Rev 1984, 91:251–268.
Rohsenow DJ, Niaura RS, Childress AR, et al.: Cue reactivity in addictive behaviors: theoretical and treatment implications. Int J Addict 1991, 25:957–993.
Childress A, Hole A, Ehrman R, et al.: Cue reactivity and cue reactivity interventions in drug dependence. NIDA Res Monogr 1993, 137:73–95.
Foltin RW, Haney M: Conditioned effects of environmental stimuli paired with smoked cocaine in humans. Psychopharmacology (Berl) 2000, 149:24–33.
Carter BL, Tiffany ST: Meta-analysis of cue reactivity in addiction research. Addiction 1999, 94:327–340.
Childress AR, Ehrman RN, McLellan AT, et al.: Can induced moods trigger drug-related responses in opiate abuse patients? J Subst Abuse Treat 1994, 11:17–23.
Cooney NL, Litt MD, Morse PA, et al.: Alcohol cue reactivity, negative mood reactivity, and relapse in treated alcoholic men. J Abnorm Psychol 1997, 106:243–250.
Sinha R, Catapano D, O’Malley S: Stress-induced craving and stress response in cocaine dependent individuals. Psychopharmacology (Berl) 1999, 142:343–351.
Sinha R, Fuse T, Aubin LR, O’Malley SS: Psychological stress, drug-related cues and cocaine craving. Psychopharmacology (Berl) 2000, 152:140–148.
Sinha R, O’Malley SS: Alcohol and craving: findings from the clinic and laboratory. Alcohol Alcohol 1999, 34:223–230.
Fox HC, Bergquist KL, Hong KI, Sinha R: Stress-induced and alcohol cue-induced craving in recently abstinent alcohol dependent individuals. Alcohol Clin Exp Res 2007, 31:395–403.
Hyman SM, Fox HC, Hong K, et al.: Stress and drug-cue-induced craving in opioid-dependent individuals in naltrexone treatment. Exp Clin Psychopharmacol 2007, 15:134–143.
Lovallo WR, Dickensheets SL, Myers DA, et al.: Blunted stress cortisol response in abstinent alcoholic and polysubstance-abusing men. Alcohol Clin Exp Res 2000, 24:651–658.
Al’absi M, Hatsukami DK, Davis G: Attenuated adrenocorticotropic responses to psychological stress are associated with early smoking relapse. Psychopharmacology (Berl) 2005, 181:107–117.
Sinha R, Talih M, Malison R, et al.: Hypothalamic-pituitary-adrenal axis and sympatho-adreno-medullary responses during stress-induced and drug cue-induced cocaine craving states. Psychopharmacology (Berl) 2003, 170:62–72.
Grant S, London ED, Newlin DB, et al.: Activation of memory circuits during cue-elicited cocaine craving. Proc. Nat Acad Sci U S A 1996, 93:12040–12045.
Childress A, Mozely PD, McElgin W, et al.: Limbic activation during cue-induced cocaine craving. Am J Psychiatry 1999, 156:11–18.
Kilts C, Schweitzer JB, Quinn CK, et al.: Neural activity related to drug craving in cocaine addiction. Arch Gen Psychiatry 2001, 58:334–341.
Kilts C, Gross RE, Ely TD, Drexler KP: The neural correlates of cue-induced craving in cocaine-dependent women. Am J Psychiatry 2004, 161:233–241.
Li CS, Kosten TR, Sinha R: Sex differences in brain activation during stress imagery in abstinent cocaine users: a functional magnetic resonance imaging study. Biol Psychiatry 2005, 57:487–494.
LeDoux JE: Emotional circuits in the brain. Annu Rev Neurosci 2000, 23:155–184.
Inglis FM, Moghaddam B: Dopaminergic innervation of the amygdala is highly responsive to stress. J Neurochem 1999, 72:1088–1094.
Sinha R, Lacadie C, Skudlarski P, et al.: Neural activity associated with stress-induced cocaine craving: a functional magnetic imaging study. Psychopharmacology (Berl) 2005, 183:171–180.
Volkow ND, Wang GJ, Telang F, et al.: Cocaine cues and dopamine in dorsal striatum: mechanism of craving in cocaine addiction. J Neurosci 2006, 26:6583–6588.
Grusser S, Wrase J, Klein S, et al.: Cue-induced activation of the striatum and medial prefrontal cortex is associated with subsequent relapse in abstinent alcoholics. Psychopharmacology (Berl) 2004, 175:296–302.
Heinz A, Siessmeier T, Wrase J, et al.: Correlation between dopamine D(2) receptors in the ventral striatum and central processing of alcohol cues and craving. Am J Psychiatry 2004, 161:1783–1789.
Fox HC, Hong KA, Siedlarz K, Sinha R: Enhanced sensitivity to stress and drug/alcohol craving in abstinent cocaine dependent individuals compared to social drinkers. Neuropsychopharmacology 2007 [Epub ahead of print].
Sinha R, Garcia M, Kemp K, et al.: Alcohol craving and subjective emotional state during stress and alcohol cue exposure in alcoholics and social drinkers. Alcohol Clin Exp Res 2005, 29:150A.
Monti P, Abrams D, Kadden R, Cooney N: Treating Alcohol Dependence: A Coping Skills Training Guide. New York: Guilford Press; 1989.
Carroll KM: A Cognitive-Behavioral Approach: Treating Cocaine Addiction. Bethesda, MD: National Institute on Drug Abuse; 1998. [NIH publication no. 98-4308.]
Carroll K, Onken LS: Behavioral therapies for drug abuse and dependence: a thirty-year progress report. Am J Psychiatry 2005, 162:1452–1460.
McKay JR, Alterman AI, Mulvaney FD, Koppenhaver JM: Predicting proximal factors in cocaine relapse and near miss episodes: clinical and theoretical implications. Drug Alcohol Depend 1999, 56:67–78.
Weiss F: Neurobiology of craving, conditioned reward and relapse. Curr Opin Pharmacol 2005, 5:9–19.
Breese GR, Chu K, Dayas CV, et al.: Stress enhancement of craving during sobriety and the risk of relapse. Alcohol Clin Exp Res 2005, 29:185–195.
Sinha R, Li CS: Imaging stress-and cue-induced drug and alcohol craving: association with relapse and clinical implications. Drug Alcohol Rev 2007, 26:25–31.
Goeders NE: The HPA axis and cocaine reinforcement. Psychoneuroendocrinology 2002, 27:13–34.
Shaham Y, Shalev U, Lu L, et al.: The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology (Berl) 2003, 168:3–20.
O’Brien CP: Anticraving medications for relapse prevention: a possible new class of psychoactive medications. Am J Psychiatry 2005, 162:1423–1431.
Sinha R, Garcia M, Paliwal P, et al.: Stress-induced cocaine craving and hypothalamic-pituitary-adrenal responses are predictive of cocaine relapse outcomes. Arch Gen Psychiatry 2006, 63:324–331.
Junghanns K, Backhaus J, Tietz U: Impaired serum cortisol stress response is a predictor of early relapse. Alcohol Alcohol 2003, 38:189–193.
Brady KT, Back SE, Waldrop AE, et al.: Cold pressor task reactivity: predictors of alcohol use among alcohol-dependent individuals with and without comorbid posttraumatic stress disorder. Alcohol Clin Exp Res 2006, 30:938–946.
Meaney MJ, Brake W, Gratton A: Environment regulation of the development of mesolimbic dopamine systems: a neurobiological mechanism for vulnerability to drug abuse? Psychoneuroendocrinology 2002, 27:127–138.
Hyman SM, Paliwal P, Sinha R: Childhood maltreatment, perceived stress, and stress-related coping in recently abstinent cocaine dependent adults. Psychol Addict Behav 2007, 21:233–238.
Caspi A, Sugden K, Moffitt TE, et al.: Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 2003, 301:386–389.
Hariri AR, Drabant E, Munoz K, et al.: A susceptibility gene for affective disorders and the response of the human amygdala. Arch Gen Psychiatry 2005, 62:146–152.
Brady KT, Sinha R: Co-occurring mental and substance use disorders: the neurobiological effects of chronic stress. Am J Psychiatry 2005, 162:1483–1493.
Nemeroff CB: The corticotropin-releasing factor (CRF) hypothesis of depression: new findings and new directions. Mol Psychiatry 1996, 1:336–342.
Holsboer F: Corticotropin-releasing hormone modulators and depression. Curr Opin Investig Drugs 2003, 41:46–50.
Scahill L, Chappell PB, Kim YS, et al.: A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder. Am J Psychiatry 2001, 158:1067–1074.
Kahn A, Mumford JP, Rogers GA, Beckford H: Double-blind study of lofexidine and clonidine in the detoxification of opiate addicts in hospital. Drug Alcohol Depend 1997, 44:57–61.
Glassman AH, Jackson WK, Walsh BT, et al.: Cigarette craving, smoking withdrawal, and clonidine. Science 1984, 226:864–866.
Sinha R, Kimmerling A, Doebrick C: Effects of lofexidine on stress-induced and cue-induced opioid craving and opioid abstinence rates: preliminary findings. Psychopharmacology (Berl) 2007, 190:569–574.
Ma SH, Teasdale JD: Mindfulness-based cognitive therapy for depression: replication and exploration of differential relapse prevention effects. J Consult Clin Psychol 2004, 72:31–40.
Bowen S, Witkiewitz K, Dillworth TM, et al.: Mindfulness meditation and substance use in an incarcerated population. Psychol Addict Behav 2006, 20:343–347.
Davis JM, Fleming MF, Bonus KA, Baker TB: A pilot study on mindfulness based stress reduction for smokers. BMC Complement Altern Med 2007, 7:2.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sinha, R. The role of stress in addiction relapse. Curr Psychiatry Rep 9, 388–395 (2007). https://doi.org/10.1007/s11920-007-0050-6
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11920-007-0050-6